EP0815110B1 - Halogenierte -carbolin-derivate, verfahren zu ihrer herstellung und verwendung dieser substanzen zur hemmung der atmungskette - Google Patents
Halogenierte -carbolin-derivate, verfahren zu ihrer herstellung und verwendung dieser substanzen zur hemmung der atmungskette Download PDFInfo
- Publication number
- EP0815110B1 EP0815110B1 EP95935329A EP95935329A EP0815110B1 EP 0815110 B1 EP0815110 B1 EP 0815110B1 EP 95935329 A EP95935329 A EP 95935329A EP 95935329 A EP95935329 A EP 95935329A EP 0815110 B1 EP0815110 B1 EP 0815110B1
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- Prior art keywords
- hal
- cooch
- mmol
- group
- taclo
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 0 Cc(c(*)c1)cc2c1[n]c1c2CCN(*)C1 Chemical compound Cc(c(*)c1)cc2c1[n]c1c2CCN(*)C1 0.000 description 6
- TYSKQWCFRUQTIM-UHFFFAOYSA-N CCC(CCN(C1)C=O)=C1NC(C)C(C)C Chemical compound CCC(CCN(C1)C=O)=C1NC(C)C(C)C TYSKQWCFRUQTIM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/99—Enzyme inactivation by chemical treatment
Definitions
- This invention relates to halogenated ⁇ -carboline derivatives, processes for their Production and use of these substances to inhibit the respiratory chain.
- NADH formed during glycolysis, fatty acid oxidation and the citrate cycle is a very high-energy molecule that has an electron pair with a high transfer potential.
- a great deal of energy is released, which is used in oxidative phosphorylation to produce ATP, the actual energy "currency" of the cell.
- Complex I of the mitochondrial respiratory chain, NADH-CoQ reductase is therefore of central importance in oxidative phosphorylation.
- the inhibitors can be administered to cultured cells or animals and, for example, drugs against diseases in which a disturbed respiratory chain plays a role could be tested on the inhibited organisms. These inhibitors are therefore an aid either to research disorders in the mitochondrial energy metabolism or to test whether certain medications counteract the respiratory chain disorder.
- the object of the present invention was therefore to use inhibitors for to provide the respiratory chain, in particular for complexes I and / or II.
- ⁇ -carboline derivatives have the general main basic structure ( I ):
- Ring C may have one, two or three double bonds.
- substituents can preferably be selected from OH-, OCH 3 -, CH 3 - F-, Cl-, Br-, I-.
- nitrogen in the indole ring is alkylated (eg -CH 3 , -C 2 H 5 , -C 3 H 7 , etc.) or acylated (eg -COCH 3 , -COC 2 H 5 , etc.) .
- Hal has the meaning of F, Cl, Br or I, the same or different could be.
- the 1-trichloromethyl heterocycles can be obtained synthetically by Pictet-Spengler ring closure from 3-indolylethylamines and chloral or by Bischler-Napieralski cyclization of 3-indolylethylamine trichloroacetamides.
- the basic structures obtained in this way can then be converted into the respective other basic structures by reduction and oxidation using suitable reagents.
- the functionalities R 1 , R 2 , R 3 and R 4 can be introduced by using appropriate starting materials (ie corresponding amine or amide derivatives). If necessary, they can also be retrofitted or modified further.
- the derivatives with functionalities in the 4-, 5- and 8-positions can also be obtained in a completely analogous manner.
- ⁇ -carboline derivatives with halogen atoms other than chlorine can be prepared using the same methods.
- the compounds with basic structure (1) will be biotransformed into the basic structures ( 2 ), ( 3 ) and / or ( 4 ), ( 5 ) by enzymatic and / or non-enzymatic oxidation reactions. Biotransformation reactions should also be considered with regard to the functional groups.
- the N- methylated compounds already show a 100% concentration in brain homogenates at concentrations ⁇ 250 ⁇ M.
- the N-alkyl compounds mentioned as preferred above can be prepared via N -alkylation.
- TaClo hydrochloride is dissolved in alcohol, preferably methanol, and reacted with NaHCO 3 and alkyl halide, alkyl sulfate or alkyl sulfonate.
- chromatography is carried out, preferably on silica gel.
- an alcoholic mineral acid solution the N-alkylated product precipitates.
- This method is of course also suitable for the preparation of the compounds with the basic structure ( 3 ) or ( 5 ), provided that starting compounds with the basic structure ( 2 ) or ( 4 ) are used.
- N -alkyl compounds can also be prepared by reduction using reducing agents such as LiAlH 4 . This is surprising since it would be expected that the X group, which is preferably CCl 3 or CBr 3 , would also be reduced.
- reducing agents such as LiAlH 4 .
- an alkylated TaClo derivative can be prepared from the corresponding acyl compound and a reducing agent.
- TaClo tryptamine in formic acid it is reacted with chloral. After heating, an alcohol, preferably methanol, is added. After the product ( N- formyl-TaClo) has crystallized, it is suspended and heated in dilute mineral acid, preferably hydrochloric acid, and alcohol, preferably methanol. After concentrating the amount of liquid, the solid obtained is filtered off.
- the basic structures ( 1 ), ( 2 ) or ( 3 ) are preferably used as starting point and oxidized with oxidizing agents, preferably KMnO 4 , or dehydrogenation catalysts.
- N-acyl compounds are reacted by reacting the corresponding compounds of the basic structures ( 1 ), ( 2 ), ( 3 ), ( 4 ) or ( 5 ) with acylating reagents, preferably acid halides or anhydrides, for example
- the corresponding compound with a CHal 3 group is preferably used and reduced with reducing agents, for example sodium borohydride in absolute methanol or with hydrogen and Pd / C as catalyst in 80 percent. Methanol.
- reducing agents for example sodium borohydride in absolute methanol or with hydrogen and Pd / C as catalyst in 80 percent. Methanol.
- a de novo synthesis from, for example, dihaloacetaldehyde and the corresponding tryptamine derivatives is also possible.
- the X group is a -C (F) 3 , -C (Cl) 3 or -C (Br) 3 group, where R 1 - R 4 have the meanings given for formula (I).
- the -C (Hal) 3 group can be a -C (F) 3 group, -C (Cl) 3 group or -C (Br) 3 group.
- R 1 , R 3 , R 4 have the meanings defined in the formula (I) and are very preferably obtained in diastereomerically pure form.
- R 1 -COCCl 3 or -COCH 2 Cl or -COCHCl 2 and X, R 2 - R 4 have the meanings given for formula (I).
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
- X = -CCl3, R1 = -CH3, R2-R4 = -H
- X = -CCl3, R1 = -CH2-C6H5, R2-R4 = -H
- X = -CCl3, R1 = -CH2-C6H5, R2 = -COOCH3, R3-R4 = -H
- X = -CCl3, R1 = -CH3, R2 = -COOCH3, R3-R4 = -H
- X = -CF3, R2-R4 = -H
- X = -CCl3, R2-R4 = -H
- X = -CBr3, R2-R4 = -H
- X = -CF3, R2 = -COOCH3, R3-R4 = -H
- X = -CCl3, R2 = -COOCH3, R3-R4 = -H
- X = -CBr3, R2 = -COOCH3, R3-R4 = -H
bevorzugt
- X = -CCl3, R1 = -C2H5, R2-R4 = -H
- X = -CCl3, R1 = -CH3, R2-R4 = -H
- X = -CBr3, R1 = -C2H5, R2-R4 = -H
- X = -CBr3, R1 = -CH3, R2-R4 = -H
- X = -CCl3, R1 = -C2H5, R2 = -COOCH3, R3-R4 = -H
- X = -CCl3, R1 = -CH3, R2 = -COOCH3, R3-R4 = -H
- X = -CBr3, R1 = -C2H5, R2 = -COOCH3, R3-R4 = -H
- X = -CBr3, R1 = -CH3, R2 = -COOCH3, R3-R4 = -H
- X = -CCl3, R2-R4 = -H
- X = -CBr3, R2-R4 = -H
- X = -CCl3, R2 = -COOCH3, R3-R4 = -H
- X = -CBr3, R2 = -COOCH3, R3-R4 = -H
- X = -CCl3, R1 = -CH3, R2-R4 = -H
- X = -CCl3, R1 = -C2H5, R2-R4 = -H
- X = -CCl3, R1 = -CH2-C6H5, R2-R4 = -H
- X = -CBr3, R1 = -CH3, R2-R4 = -H
- X = -CBr3, R1 = -C2H5, R2-R4 = -H
- X = -CBr3, R1 = -CH2-C6H5, R2-R4 = -H
- X = -CCl3, R1 = -CH3, R2 = -COOCH3, R3-R4 = -H
- X = -CCl3, R1 = -C2H5, R2 = -COOCH3, R3-R4 = -H
- X = -CCl3, R1 = -CH2-C6H5, R2 = -COOCH3, R3-R4 = -H
- X = -CBr3, R1 = -CH3, R2 = -COOCH3, R3-R4 = -H
- X = -CBr3, R1 = -C2H5, R2 = -COOCH3, R3-R4 = -H
- X = -CBr3, R1 = -CH2-C6H5, R2 = -COOCH3, R3-R4 = -H
- Julia et al., Bulletin de las Societe Chimique de France, Nr. 4, 1973, S. 1424-1426
- Bringmann et al., Liebigs Annalen der Chemie, 1991, S. 1189-1194
- GB-A-975 835
- Vecchietti et al., J. of Medicinal Chemistry, Bd. 34, 1991, S. 2624-2633
- Chemical Abstracts, Bd. 114, Nr. 5, 1991, 42 368d
- Maki et al., J. of Fluorine Chemistry, 43 (1989), S. 189-206
- Chemical Abstracts, Bd. 106, Nr. 3, 1987, 18 907t
- Chemical Abstracts, Bd. 110, Nr. 1, 1989, 2 895j.
Rl-R4 = -H
weiter bevorzugt mit:
Ausgehend von enantiomeren reinem N b-Benzyltryptophanmethylester erhält man bei der Kondensation mit Chloral in Toluol unter Rückfluß in Gegenwart katalytischer Mengen Trifluoressigsäure in hoher Stereoselektivität ausschließlich die trans-Diastereomeren. Nach Abspaltung der Benzylgruppe kann der freie Stickstoff nach den oben beschriebenen Methoden derivatisiert werden:
- NADH-Cytochrom-c-Reduktase-Test (modifiziert nach Sottocasa et al., 1967)
Hemmung der mitochondrialen Atmungskette in Rattenhirn-Homogenaten am Beispiel von N-Me-TaClo: | |
Enzym | Inhibierung bei 250 µM N-Me-TaClo |
NADH-Oxidase | 0% |
NADH-Ubichinon-1 -Reduktase | 100% |
NADH-Cytochrom-c-Reduktase | 70% |
Succinat-Cytochrom-c-Reduktase | 80% |
Succinat-Dehydrogenase | 100% |
Hemmung der mitochondrialen Atmungskette in Rattenhirn-Homogenaten durch TaClo: | ||||
Atmungsketten enzyme | Enzymaktivität (nmol/min/mg Protein) | Inhibierungsrate durch TaClo | ||
Kontrolle | 500 µM TaClo | 50 µM Rotenon | ||
Komplex I | ||||
NADH-Oxidase | 141.0 | 138.0 | - | 0% |
NADH CoQ1 Reduktase | 10.9 | 1.6 | 4.2 | 85% |
Komplex II | ||||
Succinat Dehydrogenase | 29.6 | 30.1 | - | 0% |
Komplex I/III | ||||
NADH Cyt c Reduktase | 24.6 | 14.7 | 5.7 | 40% |
Komplex II/III | ||||
Succinat Cyt c Reduktase | 11.9 | 9.2 | - | 22% |
Komplex IV | ||||
Cytochrom c Oxidase | 45.8 | 38.9 | - | 20% |
Cyt c, Cytochrom c; CoQ1, Coenzym Q1, Ubichinon-1 |
Claims (13)
- Halogenierte β-Carboline mit der Formel (I) wobei in Ring C eine, zwei oder drei Doppelbindungen vorhanden sind,X die Bedeutung -C(Hal)3, -CH(Hal)2, -CH2(Hal) oder =C(Hal)2 mit Hal = Cl, Br, I hat, unddie Substituenten R1, R2, R3 und R4 dabei folgende Bedeutungen haben:R1 : -H, eine C1-C18-Alkylgruppe (z.B. Methyl, Ethyl, Propyl, n-Butyl, iso-Butyl, tert.-Butyl usw.), -CH2-CH=CH2, -CH2-C6H5, eine Acyl- oder Aroylgruppe, mit der Maßgabe, daß R1 auch ein freies Elektronenpaar sein kann, wenn der Stickstoff an der Ausbildung einer Doppelbindung beteiligt ist.R2: -H, -COOH, -COOCH3, -COOC2H5, -COOCH2-CH=CH2, -COOCH2-C6H5, -COONH2, -CO2NR2, -CH2OAc, -CH2-OH.R3: H-, HO-, Ch3O-, C2H5O-, C6H5-CH2O-, CH3COO-, C2H5COO-,R4: H-, HO-, CH3O-, C2H5O-, C6H5-CH2O-, CH3COO-, C2H5COO-,
mit der Maßgabe, daß die folgenden Verbindungen ausgenommen sind: wobei X die Bedeutung -CCl3 oder -CH2Cl hat. wobei R2 die Bedeutung -COOH oder -COOCH3 hat, wobei X die Bedeutung -CCl3 oder CHCl2 hat, wobei X und R4 die folgenden Bedeutungen haben:X: -CCl3 und R4:H-,X: -CH2Cl und R4: H-,X: -CHBr2 und R4: CH3O-,X: -CH2Br und R4: CH3O-. - Halogenierte β-Carboline nach Anspruch 1 oder 2, wobei X eine = C(Hal)2-Gruppe mit Hal = Cl, Br, I ist und R1-R4 die in Anspruch 1 definierten Bedeutungen haben.
- Halogenierte β-Carboline nach Anspruch 2, wobei in Formel (1) die X-Gruppe eine -C(Hal)3-Gruppe mit Hal = Cl, Br, I ist und R2 = H und R1, R3, R4 die in Anspruch 1 definierten Bedeutungen haben und die Verbindungen enantiomerenrein sind.
- Verwendung von β-Carbolinen mit der Formel (I) wobei in Ring C eine, zwei oder drei Doppelbindungen vorhanden sind,X die Bedeutung -C(Hal)3, -CH(Hal)2, -CH2(Hal) oder =C(Hal)2 mitHal = Fn, Cl, Br, I hat, unddie Substituenten R1, R2, R3 und R4 dabei folgende Bedeutungen haben:R1 : -H, eine C1-C18-Alkylgruppe (z.B. Methyl, Ethyl, Propyl, n-Butyl, iso-Butyl, tert.-Butyl usw.), -CH2-CH=CH2, -CH2-C6H5, eine Acyl- oder Aroylgruppe, mit der Maßgabe, daß R1 auch ein freies Elektronenpaar sein kann, wenn der Stickstoff an der Ausbildung einer Doppelbindung beteiligt ist.R2: -H, -COOH, -COOCH3, -COOC2H5, -COOCH2-CH=CH2, -COOCH2-C6H5, -COONH2, -CO2NR2, -CH2OAc, -CH2-OH,R3: H-, HO-, CH3O-, C2H5O-, C6H5-CH2O-, CH3COO-, C2H5COO-R4: H-, HO-, CH3O-, C2H5O-, C6H5-CH2O-, CH3COO-, C2H5COO-,
- Verwendung nach Anspruch 5, wobei der Komplex I und/oder II der Atmungskette gehemmt wird.
- Verwendung nach einem der Ansprüche 5-7, wobei in Formel (I) R1-R4 = H und X = C(Cl)3 oder C(Br)3 oder C(F)3 ist.
- Verwendung nach einem der Ansprüche 5-8, wobei X eine =C(Hal)2-Gruppe mit Hal = F, Cl, Br, I ist und R1-R4 die in Anspruch 5 definierten Bedeutungen haben.
- Verwendung halogenierter β-Carboline nach Anspruch 7, wobei in Formel (1) die X-Gruppe eine -C(Cl)3-Gruppe, -C(Br)3-Gruppe oder -C(F)3-Gruppe ist und R1-R4 die in Anspruch 5 definierte Bedeutung haben.
- Verwendung halogenierter β-Carboline in enantiomerenreiner Form nach Anspruch 7, wobei in Formel (1) die X-Gruppe eine -C(Hal)3-Gruppe mit Hal = F, Cl, Br, I ist und R2 = H und R1, R3, R4 die in Anspruch 7 definierte Bedeutung haben.
- Verwendung halogenierter β-Carboline nach Anspruch 7, wobei der Stickstoff im Indolring alkyliert oder acyliert ist und X, R1-R4 die in Anspruch 5 definierten Bedeutungen haben.
- Verwendung halogenierter β-Carboline nach einem der Ansprüche 5-12 mit OH-, OCH3-, CH3, F-, Cl-, Br- und I-Substituenten in den Positionen 4 und/oder 5 und/oder 8 des β-Carbolingerüsts, wobei X, R1-R4 die in Anspruch 5 definierten Bedeutungen haben.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4436190 | 1994-10-10 | ||
DE4436190A DE4436190A1 (de) | 1994-10-10 | 1994-10-10 | Halogenierte ß-Carbolin-Derivate, Verfahren zu ihrer Herstellung und Verwendung dieser Substanzen zur Hemmung der Atmungskette |
PCT/DE1995/001403 WO1996011197A1 (de) | 1994-10-10 | 1995-10-10 | HALOGENIERTE β-CARBOLIN-DERIVATE, VERFAHREN ZU IHRER HERSTELLUNG UND VERWENDUNG DIESER SUBSTANZEN ZUR HEMMUNG DER ATMUNGSKETTE |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0815110A1 EP0815110A1 (de) | 1998-01-07 |
EP0815110B1 true EP0815110B1 (de) | 1999-04-28 |
Family
ID=6530403
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP95935329A Expired - Lifetime EP0815110B1 (de) | 1994-10-10 | 1995-10-10 | Halogenierte -carbolin-derivate, verfahren zu ihrer herstellung und verwendung dieser substanzen zur hemmung der atmungskette |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0815110B1 (de) |
AT (1) | ATE179418T1 (de) |
AU (1) | AU3740395A (de) |
DE (2) | DE4436190A1 (de) |
WO (1) | WO1996011197A1 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6864253B2 (en) | 2000-05-17 | 2005-03-08 | Orth-Mcneil Pharmaceutical, Inc. | Benzo[4,5]thieno[2,3-c]pyridine and Benzo[4,5]furo[2,3-c]pyridine Derivatives Useful as Inhibitors of Phosphodiesterase |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4895847B2 (ja) | 2007-02-08 | 2012-03-14 | アイシン精機株式会社 | 瞼検出装置及びプログラム |
AU2009204048B2 (en) | 2008-01-11 | 2013-08-01 | Albany Molecular Research, Inc. | (1-azinone) -substituted pyridoindoles as MCH antagonists |
US8637501B2 (en) | 2009-07-01 | 2014-01-28 | Albany Molecular Research, Inc. | Azinone-substituted azepino[b]indole and pyrido-pyrrolo-azepine MCH-1 antagonists, methods of making, and use thereof |
US9073925B2 (en) | 2009-07-01 | 2015-07-07 | Albany Molecular Research, Inc. | Azinone-substituted azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine MCH-1 antagonists, methods of making, and use thereof |
WO2011003007A1 (en) | 2009-07-01 | 2011-01-06 | Albany Molecular Research, Inc. | Azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine mch-1 antagonists, methods of making, and use thereof |
US8618299B2 (en) | 2009-07-01 | 2013-12-31 | Albany Molecular Research, Inc. | Azinone-substituted azapolycycle MCH-1 antagonists, methods of making, and use thereof |
US8993765B2 (en) | 2010-12-21 | 2015-03-31 | Albany Molecular Research, Inc. | Tetrahydro-azacarboline MCH-1 antagonists, methods of making, and uses thereof |
WO2012088038A2 (en) | 2010-12-21 | 2012-06-28 | Albany Molecular Research, Inc. | Piperazinone-substituted tetrahydro-carboline mch-1 antagonists, methods of making, and uses thereof |
CN113416187B (zh) | 2013-03-14 | 2024-07-19 | 奥斯菲治疗有限公司 | 促进骨生长的烷基胺骆驼蓬碱衍生物 |
MX2021001710A (es) | 2018-08-14 | 2021-06-08 | Osteoqc Inc | Compuestos de fluoro ?-carbolina. |
EP3836923A4 (de) | 2018-08-14 | 2022-05-18 | Osteoqc Inc. | Pyrrolo-dipyridinverbindungen |
CN112758902B (zh) * | 2021-01-06 | 2022-01-28 | 西南科技大学 | 用于高效析氧反应的优化电子构型Co4N纳米片的制备方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES273769A1 (es) * | 1961-01-18 | 1962-06-01 | Geigy Ag J R | Procedimiento para la preparaciën de nuevos derivados de amidas de acido beta-carbolin-carboxilico |
JPH07110859B2 (ja) * | 1987-01-20 | 1995-11-29 | 工業技術院長 | 1−トリフルオロメチルカルボリン誘導体、その製造法およびそれを有効成分とする植物病害防除剤 |
DE4212529A1 (de) * | 1992-04-10 | 1993-10-14 | Schering Ag | Verwendung von µ-Carbolinen als nicht-kompetitive Glutamat-Antagonisten |
-
1994
- 1994-10-10 DE DE4436190A patent/DE4436190A1/de not_active Ceased
-
1995
- 1995-10-10 AT AT95935329T patent/ATE179418T1/de not_active IP Right Cessation
- 1995-10-10 DE DE59505800T patent/DE59505800D1/de not_active Expired - Fee Related
- 1995-10-10 EP EP95935329A patent/EP0815110B1/de not_active Expired - Lifetime
- 1995-10-10 WO PCT/DE1995/001403 patent/WO1996011197A1/de active IP Right Grant
- 1995-10-10 AU AU37403/95A patent/AU3740395A/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6864253B2 (en) | 2000-05-17 | 2005-03-08 | Orth-Mcneil Pharmaceutical, Inc. | Benzo[4,5]thieno[2,3-c]pyridine and Benzo[4,5]furo[2,3-c]pyridine Derivatives Useful as Inhibitors of Phosphodiesterase |
Also Published As
Publication number | Publication date |
---|---|
AU3740395A (en) | 1996-05-02 |
DE59505800D1 (de) | 1999-06-02 |
WO1996011197A1 (de) | 1996-04-18 |
DE4436190A1 (de) | 1996-04-11 |
ATE179418T1 (de) | 1999-05-15 |
EP0815110A1 (de) | 1998-01-07 |
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